In the area of sensing, vibrating mechanical structures, for example, microcantilever arrays find various applications based on advantages such as lower detection limits due to miniaturization, the ability of shape optimization of cantilevers, the ability to selectively place functionalized regions on the these cantilevers (also interchangeably called “microcantilevers”), and the possibility of working on large arrays which can be integrated with optics and electronics.
Some of the disadvantages of these currently known types of sensors are; that they require electrical connections (also called electrical conductors) to couple the sensor to a detector, limited optical detection options, limitations to liquid or gas phase detection, sensors that use frail readout components (for example, Doppler vibrometry), readouts that can be affected by refractive index variations due to monitoring of the deflection, sensors with no immunity against environmental noise, and the inability to heat the cantilever/samples during sensing. Further, it is believed that current alternatives to parallel sensing are limited to laboratory use only. It is therefore desirable to have a fieldable, label-free demonstrator, which is missing due to the lack of various components including a suitable readout mechanism that can be utilized in an array setting, a package that would protect functionalized surfaces during shelf life, which usually requires handling of liquids, and an integrated approach that would allow disposal of certain components, whereas others remain for the next use (for example, disposable cartridges containing the MEMS sensor array).
One objective of this invention is to enable a MEMS sensor array having a sensor array that is miniaturized, highly selective, highly sensitive, parallel, label-free and/or portable. Such a sensor array will provide a valuable tool for point-of-care diagnostics and chemical sensing with its capabilities of a single analyte or a multianalyte screening and data processing. It is a further objective of these sensor arrays to increase sensitivity and specificity to possibly increase the likelihood of early diagnosis as well as the suitability of treatment assistance, such as dosage advice. It is envisioned that this may lead to increased effectiveness of doctor-patient interaction and personalized guidance. It is believed that such systems that meet the demands of parallel, label-free, and highly selective sensing do not exist today as microsystem technologies and readout methods cannot meet expectations for various reasons including: robustness issues associated with functional surfaces and the lack of a truly integrated, array-compatible readout techniques. Alternatively, it is believed that microarray technologies can offer parallel and selective detection, but are not fieldable as they require expertise to run and maintain and require expensive infrastructure due to complex labeling and sensing methods. While many fieldable applications, such as pregnancy test kits or the glucose sensor exist, these applications are limited to one kind of species and lack parallel detection capability.
the sensor array platform is highly innovative and versatile and has inspired by the novel uses. For example, for the point-of-care diagnostics applications it is envisioned that a microsystem-based parallel sensor array (2 to 64 channels and more), can be used for various species for shifts in resonance frequency of an array of cantilevers will be monitored as an indication of mass accumulation. In this example, detection of frequency shifts will be carried out through a novel integrated optoelectronic chip. Sensitivity in the range of 0.1 to 1000 ng/ml with better than 25% reproducibility is aimed.
Additionally, possible uses of this invention include liquid phase detection of disease from body fluids (e.g., blood, serum, urine, or saliva), gas phase detection as an artificial nose sensor serving as air pollutants detector airborne disease diagnosis tool, warfare pathogens detector and explosives trace detector. It is envisioned that one can use the apparatus to detect substances that are characterized with low vapor pressure and hence are hard to detect; for example, to identify explosive traces, possibly with a potential sensitivities capable of sensing masses on the order of femtograms. Further refinements, such as a pre-concentrator increase the vapor pressure, may be proposed to further increase sensitivities. Another novel aspect of the invention is identifying the material not only by its simple adsorption signature, but also through adsorption/desorption isotherms that can allow identifying, with higher accuracy, the substance or the components of a mixture. Additionally, it is believed that in an aqueous medium, the invention will allow parallel, fast, real-time monitoring of a large number of analytes (e.g., proteins, pathogens, and DNA strands) without any need for labeling, and, therefore, be ideal for the targets screening in drug discovery process, or as a promising alternative to current DNA and protein micro array chips. Using such a label-free apparatus may decrease the number of preparation stages and shorten diagnosis time. It is proposed that one can investigate DNA sequences, successful results will be the positive detection of various mutations in human DNA (e.g., sickle cell anemia, -thallesemia) in parallel.
This invention demonstrates a highly parallel label-free detection of (bio/chem) agents in a robust, miniaturized package using multiple disciplines including integrated photonics, VLSI, and Micro/Nano system technologies to develop a versatile sensor array with breakthrough performance.
each sensor is typically located on a MEMS sensor array operates by monitoring the resonant frequency of the vibrating mechanical structures (also called cantilevers or microcantilevers). Output of a sensor is the change in resonant frequency in response to accumulated mass on the cantilever due to a specific binding event. The array of cantilevers may be actuated by an actuating means; for example, electromagnetic force means; piezoelectric force; electric force; electrostatic force means and combinations thereof. The most preferred actuating means is a single electro-coil that carries a superposed drive current waveform. Preferably Optical feedback from a mechanism to sense light coupled with each sensor is used for detection of specific binding events and also for closed-loop control of the cantilevers at resonance. More preferably, damping can be tuned by closed-loop control electronics allowing sharp resonance peaks (high-Q) even in liquid media. In a preferred embodiment, frequency resolution is inherently higher compared to other read-out techniques such as the piezoresistive or capacitive methods.
preferably, the MEMS chip contains the functionalization layer on magnetic structural layer (for example, Nickel). More preferably, the location on the cantilever of the functionalized layer can be chosen to maximize the resonant frequency shift per added unit mass. In a preferred embodiment, the novel structure of the cantilevers includes a diffraction grating in the form of simple slits and/or heating elements. The MEMS sensor array (also called a MEMS chip) is preferably envisioned to be disposable and replaceable in future products; for example, as a disposable cartridge containing a MEMS sensor array to be coupled with a detector apparatus containing an actuating means (also sometimes called an actuator). This preferred embodiment would leave the actuator and electronics layers intact for reuse. Preferably, the MEMS chip is a passive component with no electronic link (also called an electrical conductor) to the detector apparatus. In this preferred embodiment this will facilitate work in fluidic environments, since less isolation, coupling, and stiction issues need to be considered. Furthermore, the preferred embodiment includes the integration of electronics and optics coupled with a passive component to provide ease and flexibility of use compared to a direct integration of the MEMS layer with IC detection apparatus. Finally in a preferred embodiment, magnetic actuation can be carried out remotely through an external electromagnetic coil on the MEMS chip. It is believed that sensitivity levels achieved in mass measurements will directly be reflected by detection sensitivity of the analytes of interest. Additionally, the type of surface functionalization utilized on the cantilever surfaces will determine the field of application, e.g., Human Kappa Opioid receptor (HKOR) is utilized for the detection of narcotics. In a preferred embodiment it is believed that a minimum mass detection limit of 500 femtograms or less may be achieved through discrete optics, electronics, and an electromagnet. Preferably, integration of discrete components and further miniaturization will substantially improve the minimum detection limit, sensitivity, parallelism, and robustness of the apparatus and will meet the challenges of label-free and parallel detection in a portable device.